Homo sapiens · seed P15056 · 766 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P15056 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 3.10.20.90 CATH 2.30.30.40 CATH 3.30.200.20 CATH 3.30.505.10 CATH 1.10.510.10 SCOP 8034476 SCOP 8034606 SCOP 8035244 SCOP 8036660 SCOP 8041589 SCOP 8036665 SCOP 8033424 SCOP 8039520 SCOP 8069157 SCOP 8036479 SCOP 8069203 SCOP 8040719 SCOP 8072703 SCOP 8040157 SCOP 8062400 SCOP 8069247 SCOP 8032830 SCOP 8069199 SCOP 8069261 SCOP 8069273 SCOP 8035661 SCOP 8036656 SCOP 8032837 RCSB 4XV1 PDBe
CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.
Every figure here is counted over the whole family rather than quoted from one entry.
4XV1, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.
How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.
412 distinct constructs across 1,041 entries. 988 polymer entities differ from the UniProt canonical sequence in some way, 27 carry a recognised expression tag and 2 carry a fusion partner.
"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.
| Entities | Length | Best (Å) | Best entry | What was made |
|---|---|---|---|---|
| 61 | 306 | 0.98 | 6Q7D | residues 595-900; E595G |
| 32 | 286 | 1.80 | 7WF5 | residues 248-533; S248G, K249H, P250M |
| 21 | 454 | 1.65 | 5H0B | residues 72-526; 1 internal deletion; I73A, R74M, E75G +6 more |
| 18 | 301 | 2.00 | 2OIB | residues 160-460 |
| 17 | 307 | 2.55 | 4E26 | residues 424-726; 4-residue insertion after 428; R424M, E425D, K427G +3 more |
| 15 | 308 | 1.90 | 6VGL | residues 825-1132; M825H, R826H, I827H +12 more |
| 14 | 285 | 1.99 | 3AC1 | residues 225-509 |
| 14 | 1370 | 3.24 | 8X06 | 1 internal deletion |
| 11 | 302 | 1.65 | 2VWX | residues 598-899; Y774E |
| 11 | 308 | 1.87 | 9R9K | residues 153-460; P153G |
| 11 | 309 | 1.75 | 4XMO | residues 1048-1356; V1352H, N1353H, A1354H +2 more |
| 11 | 1372 | 3.10 | 7SL7 | matches the canonical sequence |
| 10 | 283 | 2.47 | 7M0X | residues 441-723; L441G, R443G |
| 10 | 286 | 2.20 | 3G5D | residues 248-533; S248G, K249H, P250M +1 more |
| 10 | 299 | 1.75 | 7B3Q | residues 1048-1346; Q1048G |
| 10 | 309 | 1.54 | 9T0B | residues 1038-1346; D1228V |
| 10 | 316 | 1.30 | 8BXH | residues 825-1132; 8-residue insertion after 835; R826H, I827H, G828H +8 more |
| 10 | 361 | 1.35 | 4P5Q | residues 574-947; 1 internal deletion; H574M, A576S, D577S +14 more |
| 9 | 286 | 1.90 | 6HVE | residues 248-533; S248G, K249H, P250M +2 more |
| 9 | 306 | 1.40 | 3ZCL | residues 1050-1355; T1050M, Y1349H, V1350H +4 more |
| 9 | 307 | 1.80 | 8UCC | residues 154-460 |
| 9 | 318 | 2.00 | 6DBK | residues 861-1182; 1 internal deletion; T861M, I862A, L863H +22 more |
| 8 | 304 | 1.73 | 9NA5 | residues 157-460; S157G, L158A, E159M |
| 8 | 305 | 1.89 | 8SCE | residues 156-460; K156G, S157A, L158M +1 more |
| 8 | 309 | 2.16 | 7Y4T | residues 1038-1346 |
Showing the 25 most-used of 412.
Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".
| Oligomeric state | Chains | Entries | Share |
|---|---|---|---|
| monomeric | 1 | 773 | 74.3% |
| dimeric | 2 | 151 | 14.5% |
| tetrameric | 4 | 51 | 4.9% |
| trimeric | 3 | 26 | 2.5% |
| hexameric | 6 | 23 | 2.2% |
| pentameric | 5 | 10 | 1.0% |
| octameric | 8 | 4 | 0.4% |
| decameric | 10 | 2 | 0.2% |
623 entries have the depositor's assembly corroborated by PISA, 370 carry the depositor's word alone and 48 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 35 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1GAG, 1P4O, 1U5Q, 1U5R, 2GCD, 2OU7, 2OWB, 2RKU, 2ZM3, 3EFJ, 3EFK, 3EQP, 3EQR, 3ETA, 3F5P, 3II5, 3Q96, 3SXR, 3THB, 3U6H.
Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.
| Domain | Source | Span (seed) | Chains |
|---|---|---|---|
| Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 | CATH 3.10.20.90 | 162–236 | 17 |
| SH3 Domains | CATH 2.30.30.40 | 455–516 | 25 |
| Phosphorylase Kinase; domain 1 | CATH 3.30.200.20 | 462–551 | 659 |
| SH2 domain | CATH 3.30.505.10 | 517–618 | 25 |
| Transferase(Phosphotransferase) domain 1 | CATH 1.10.510.10 | 554–752 | 692 |
| Ubiquitin-like | SCOP2B 8034476 | 160–236 | 20 |
| Protein kinase-like (PK-like) | SCOP2B 8034606 | 452–753 | 20 |
| Protein kinase-like (PK-like) | SCOP2B 8035244 | 453–724 | 109 |
| Protein kinase-like (PK-like) | SCOP2B 8036660 | 454–724 | 34 |
| SH3-domain | SCOP2B 8041589 | 456–516 | 23 |
| Protein kinase-like (PK-like) | SCOP2B 8036665 | 457–728 | 70 |
| Protein kinase-like (PK-like) | SCOP2B 8033424 | 457–733 | 26 |
ANP54 entries
GNP20 entries
ADP14 entries
STU12 entries
ATP12 entries
AGS12 entries
LCJ10 entries
ACP9 entries
1N18 entries
A1AHE8 entries
RXT7 entries
VSE5 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| SO4 | ion | Sulfate Ion | 104 | 1.31 |
| MG | ion | Magnesium Ion | 103 | 1.20 |
| GOL | cryoprotectant | Glycerol | 71 | 1.45 |
| CL | ion | Chloride Ion | 68 | 1.30 |
| EDO | cryoprotectant | 1,2-Ethanediol | 66 | 1.04 |
| ANP | cofactor | Phosphoaminophosphonic Acid-Adenylate Ester | 54 | 1.25 |
| ZN | ion | Zinc Ion | 41 | 1.71 |
| CA | ion | Calcium Ion | 30 | 1.90 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 21 | 1.40 |
| GNP | cofactor | Phosphoaminophosphonic Acid-Guanylate Ester | 20 | 1.40 |
| ACT | cryoprotectant | Acetate Ion | 17 | 1.80 |
| ADP | cofactor | Adenosine-5'-Diphosphate | 14 | 1.61 |
| NA | ion | Sodium Ion | 13 | 1.40 |
| STU | ligand | Staurosporine | 12 | 2.00 |
| ATP | cofactor | Adenosine-5'-Triphosphate | 12 | 1.52 |
| AGS | cofactor | Phosphothiophosphoric Acid-Adenylate Ester | 12 | 1.46 |
| LCJ | ligand | 5-[(2-Fluoro-4-Iodophenyl)amino]-N-(2-Hydroxyethoxy)imidazo[1,5- | 10 | 2.59 |
| ACP | cofactor | Phosphomethylphosphonic Acid Adenylate Ester | 9 | 1.75 |
| BME | buffer | Beta-Mercaptoethanol | 9 | 1.20 |
| 1N1 | ligand | N-(2-Chloro-6-Methylphenyl)-2-({6-[4-(2-Hydroxyethyl)piperazin-1 | 8 | 1.16 |
Parsed from the free text 883 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 901
entries that recorded anything at all.
Median pH 7.0
(range 0.0 to 10.5).
1,041 entries carry a wwPDB validation report: 284 clean, 491 worth a check and 266 with something to explain. Median clashscore 5.33, median RSRZ outliers 5.65%, median R-free minus R-work 0.041. 994 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 917 | 0.98 | 796 | 100% |
| Gallus gallus | 72 | 1.78 | 64 | 35% |
| Mus musculus | 31 | 1.54 | 9 | 37% |
| Danio rerio | 11 | 2.30 | 8 | 26% |
| Rattus norvegicus | 4 | 2.10 | 2 | 37% |
| synthetic construct | 2 | 2.05 | 2 | 35% |
| Schistosoma mansoni | 1 | 3.07 | 1 | 28% |
| Saccharomyces cerevisiae | 1 | 3.10 | 0 | 19% |
| Kluyveromyces marxianus | 1 | 3.18 | 0 | 17% |
| Drosophila melanogaster | 1 | 3.32 | 1 | 37% |
766 residues, numbered every ten. Every identity figure in this document is measured against this sequence.
active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions
Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.
One record per paper, not per entry.
| Year | Citation |
|---|---|
| 2026 | Molecular Basis of c‐MET Inhibition by Approved Small Molecule Drugs: A Structural Perspective. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00713 |
| 2026 | Structural insights into multitargeting Mycobacterium tuberculosis Pkn kinases. Microbiol Spectr doi:10.1128/spectrum.00049-26 |
| 2026 | Discovery of the Orally Bioavailable Isoform Selective Janus Kinase 1 (JAK1) Compound Povorcitinib (INCB054707) for the Treatment of Inflammatory and Autoimmune Diseases. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03753 |
| 2026 | Janus kinase 2 activation loop as a regulator of catalysis and trans-activation. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2026.153276 |
| 2026 | Disrupted molecular glue complex drives RAS inhibitor resistance. Cell doi:10.1016/j.cell.2026.03.031 |
| 2026 | Examination of Noncanonical Kinase Hinge Binders Leads to Thiadiazoles as Potent IRAK4 Inhibitors. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00602 |
| 2026 | Structural basis for selective and potent degradation of IRAK4 by KT-474. Nat Commun doi:10.1038/s41467-026-74105-w |
| 2026 | Fyn-Saracatinib Complex Structure Reveals an Active State-like Conformation. Int J Mol Sci doi:10.3390/ijms27031143 |
| 2026 | De Novo Discovery of Nonstandard Thioisoindole-Bridged Bicyclic Peptides Targeting Traf2- and NCK-Interacting Kinase. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.2417165 |
| 2026 | Mechanism of MEK1 phosphorylation by the N-terminal acidic motif-mediated asymmetric BRAF dimer. Mol.Cell doi:10.1016/j.molcel.2026.06.039 |
| 2026 | Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03664 |
| 2026 | Discovery of 2H-Pyrrolo[3,4‐ c ]pyridin-3-one Derivatives as Type-III c‐MET Inhibitors Enabled by Free-Energy Perturbation Calculations. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00158 |
| 2026 | Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy. Nat Commun doi:10.1038/s41467-026-69884-1 |
| 2026 | High-resolution cryo-EM structures of small protein-ligand complexes near the theoretical size limit. Nat Commun doi:10.1038/s41467-026-71934-7 |
| 2026 | The MEK-RAF molecular glue IK-595 has potent antitumor activity across RAS/MAPK pathway-altered cancers. Nat Cancer doi:10.1038/s43018-025-01081-3 |
| 2026 | Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2. Nat Commun doi:10.1038/s41467-026-73851-1 |
| 2025 | Discovery of Edecesertib (GS-5718): A Potent, Selective Inhibitor of IRAK4. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00463 |
| 2025 | Generation of a potent & selective series of IRAK4 inhibitors based on a structure based, hybridization approach. Bioorg.Med.Chem. doi:10.1016/j.bmc.2025.118333 |
| 2025 | Polo-like kinase 1-inhibitor co-complex structures via the surface-entropy reduction approach and a DARPin-assisted approach. Acta Crystallogr D Struct Biol doi:10.1107/S2059798325009325 |
| 2025 | Characterization of Bozitinib as a potential therapeutic agent for MET-amplified gastric cancer. Commun Biol doi:10.1038/s42003-025-07490-5 |
| 2025 | Harnessing free energy calculations for kinome-wide selectivity in drug discovery campaigns with a Wee1 case study. Nat Commun doi:10.1038/s41467-025-62722-w |
| 2025 | Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation. Nat Commun doi:10.1038/s41467-025-63227-2 |
| 2025 | Characterization and inhibitor sensitivity of ARAF, BRAF, and CRAF kinases. J.Biol.Chem. doi:10.1016/j.jbc.2025.110800 |
| 2025 | BRAF oncogenic mutants evade autoinhibition through a common mechanism. Science doi:10.1126/science.adp2742 |
| 2025 | Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2415807122 |
| 2025 | Discovery of KIN-8741, a Highly Selective Type IIb c-Met Kinase Inhibitor with Broad Mutation Coverage and Quality Drug-Like Properties for the Treatment of Cancer. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00834 |
| 2025 | Tuning insulin receptor signaling using de novo-designed agonists. Mol.Cell doi:10.1016/j.molcel.2025.09.020 |
| 2025 | Conformational landscape adaptations enable processive phosphorylation by Src family kinases. Science doi:10.1126/science.adw8310 |
| 2024 | Functional and Structural Characterization of Clinical-Stage Janus Kinase 2 Inhibitors Identifies Determinants for Drug Selectivity. J.Med.Chem. doi:10.1021/acs.jmedchem.4c00197 |
| 2024 | Discovery of Pyrazolopyrazines as Selective, Potent, and Mutant-Active MET Inhibitors with Intracranial Efficacy. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01232 |
| 2024 | Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties. Sci Adv doi:10.1126/sciadv.adj4137 |
| 2024 | In Retrospect: Root-Cause Analysis of Structure-Activity Relationships in IRAK4 Inhibitor Zimlovisertib (PF-06650833). Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00036 |
| 2024 | Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.4c00411 |
| 2024 | The Discovery of 7-Isopropoxy-2-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)- N -(6-methylpyrazolo[1,5- a ]pyrimidin-3-yl)imidazo[1,2- a ]pyrimidine-6-carboxamide (BIO-7488), a Potent, Selective, and CNS-Penetrant IRAK4 Inhibitor for the Treatment of Ischemic Stroke. J.Med.Chem. doi:10.1021/acs.jmedchem.3c02226 |
| 2024 | Cocrystallization of the Src-Family Kinase Hck with the ATP-Site Inhibitor A-419259 Stabilizes an Extended Activation Loop Conformation. Biochemistry doi:10.1021/acs.biochem.4c00323 |
| 2024 | Identification of the Clinical Candidate PF-07284890 ( ARRY-461 ), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer. J.Med.Chem. doi:10.1021/acs.jmedchem.4c00998 |
| 2024 | A Tiny Pocket Packs a Punch: Leveraging Pyridones for the Discovery of CNS-Penetrant Aza-indazole IRAK4 Inhibitors. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00102 |
| 2024 | Discovery of BIO-8169─A Highly Potent, Selective, and Brain-Penetrant IRAK4 Inhibitor for the Treatment of Neuroinflammation. J.Med.Chem. doi:10.1021/acs.jmedchem.4c00560 |
| 2024 | The Pan-RAF-MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS-MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers. Cancer Discov doi:10.1158/2159-8290.CD-24-0139 |
| 2024 | Discovery of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates Targeting MYD88 Mutant Diffuse Large B-Cell Lymphoma. J.Med.Chem. doi:10.1021/acs.jmedchem.3c01823 |